Although the synaptic organization and information processing of the vertebrate retina is fairly well understood, little is known about the manner by which specific synaptic connections are formed between retinal neurons. The study of retinal development, during which cellular differentiation and synapse formation occur, offers an opportunity to examine the sequence of events leading to the formation of a functional retina. Another interesting system for such studies is retinal regeneration of the adult newt in which the destruction of the original retina leads to the formation of a new and functional retina. The purpose of this research proposal is to use both conventional and recently developed methods to study retinal development and regeneration, and to correlate our results with the findings of other investigators. There are five main objectives: 1) Retinal degeneration and regeneration in adult newts will be induced by serving all the vascular and neural connections with the eye. Electroretinograms from isolated eyes at different stages of regeneration will then be recorded (Lam, 1977b.). Immediately after recording, each eye will be used for measuring DNA, RNA, protein or transmitter syntheses by radiochemical methods or for electron microscopic, histochemical or autoradiographic studies. 2) Transmitter syntheses in developing frog and xenopus tadpole and rabbit retinas will be studied and be correlated with known morphological and physiological findings. 3) The development of the goldfish retina, especially the formation of photoreceptor-horizontal cell connections will be studied by electron microscopy, autoradiography of H3 GABA uptake and NBT histochemistry. 4) The morphological and biochemical changes in pigment epithilial cells during their dedifferentiation and differentiation into a regenerating retinal rudiment will be studied. 5) The sequence in which retinal cells mature during development and regeneration will be compared to determine if the patterns of maturation are different.